We have continued our investigation into the relationship between cortical and subcortical systems, particularly between catecholamines in the prefrontal cortex (PFC) and the nucleus accumbens and corpus striatum. In studies involving lesions of the medial prefrontal cortex we have focused on the ability of different types of stressors to alter both dopamine linked behaviors and biochemical indices of dopamine function, at a time (more than 6 weeks postoperatively) when baseline indices are not different between sham and lesioned animals. A variety of pharmacological and environmental stressors appear to attenuate locomotor exploration of a novel environment in rats with frontal lesions. Moreover, the lesion appears to alter the biochemical response of dopamine systems to mild chronic stress. One week following termination of a 7 day series of daily vehicle injections, rats with frontal lesions show enhancement of presynaptic dopaminergic indices in the nucleus accumbens. Administration of D1 and D2 agonists an antagonists suggest an upregulation of striatal and accumbal dopamine receptors endures several months following frontal lesions. In conclusion, the prefrontal cortex clearly influences catecholamine turnover and associated behaviors in subcortical ares and this influence becomes particularly important under stressful conditions.